Background Regular physical activity supports healthy behavior and contributes to the reduction of preventable diseases. Students in their social transition period are the ideal groups for interventions. The higher education period, associated with demanding changes and poor time management, results in a low level of physical activity. In this age, social media usually are a suitable channel of communication and multicomponent interventions are the most desirable. It has not been sufficiently investigated how effective a Web-based approach is among university students when it comes to physical activity in the long-term period. We combined a Web-based approach with motivational interviews and tested these two interventions together and separate to assess their impact on improving the physical activity of medical students 1 year after the intervention. Methods All 514 first-year students at the Faculty of Medicine in Belgrade were invited to fill in a baseline questionnaire. Also, they underwent measurement of weight, height and waist circumference. After that, students selected a 6 months intervention according to their preference: Intervention through social media (Facebook) (Group 1) or combined with a motivational interview (Group 2). Group 3 consisted of students without any intervention. One year after completion of the 6 months intervention period, all students were invited to a second comprehensive assessment. Analyses were performed employing a wide range of statistical testing, including direct logistic regression, to identify determinants of increased physical activity measured by an average change of Metabolic Equivalent of Task (MET). This outcome measure was defined as the difference between the values at baseline and one year after completion of the 6 months intervention period. Results Due to a large number of potential determinants of the change of MET, three logistic regression models considered three groups of independent variables: basic socio-demographic and anthropometric data, intervention and willingness for change, and health status with life choices. The only significant model comprised parameters related to the interventions (p < 0.001). It accurately classified 73.5% of cases. There is a highly significant overall effect for type of intervention (Wald = 19.5, df = 2, p < 0.001) with high odds for the increase of physical activity. Significant relationship between time and type of intervention also existed (F = 7.33, p < 0.001, partial η² = 0.091). The influence of both factors (time and interventions) led to a change (increase) in the dependent variable MET. Conclusion Our study confirmed the presence of low-level physical activity among students of medicine and showed that multicomponent interventions have significant potential for positive change. The desirable effects of the Web-based intervention are higher if an additional booster is involved, such as a motivational interview.